BUFFALO, N.Y. -- Animals that are socially isolated for
prolonged periods make less myelin in the region of the brain
responsible for complex emotional and cognitive behavior,
researchers at the University at Buffalo and Mt. Sinai School of
Medicine report in Nature Neuroscience online.

The research sheds new light on brain plasticity, the brain's
ability to adapt to environmental changes. It reveals that neurons
aren't the only brain structures that undergo changes in response
to an individual's environment and experience, according to one of
the paper's lead authors, Karen Dietz, PhD, research scientist in
the Department of Pharmacology and Toxicology in the UB School of
Medicine and Biomedical Sciences.

Dietz did the work while a postdoctoral researcher at Mt. Sinai
School of Medicine; Jia Liu, PhD, a Mt. Sinai postdoctoral
researcher, is the other lead author. Patrizia Casaccia, MD, PhD,
Mt. Sinai professor of genetics and genomic sciences, neuroscience
and neurology, is corresponding author.

The paper notes that changes in the brain's white matter, or
myelin, have been seen before in psychiatric disorders, and
demyelinating disorders have also had an association with
depression. Recently, myelin changes were also seen in very young
animals or adolescents responding to environmental changes.

"This research reveals for the first time a role for myelin in
adult psychiatric disorders," Dietz says. "It demonstrates that
plasticity in the brain is not restricted to neurons, but actively
occurs in glial cells, such as the oligodendrocytes, which produce
myelin."

Myelin is the crucial fatty material that wraps the axons of
neurons and allows them to signal effectively. Normal nerve
function is lost in demyelinating disorders, such as MS and the
rare, fatal, childhood disease, Krabbe's disease.

This paper reveals that the stress of social isolation disrupts
the sequence in which the myelin-making cells, the
oligodendrocytes, are formed.

In the experiment, adult mice, normally social animals, were
isolated for eight weeks to induce a depressive-like state. They
were then introduced to a "novel" mouse, one they hadn't seen
before; while mice are normally highly motivated to be social,
those who had been socially isolated did not show any interest in
interacting with the new mouse, a model of social avoidance and
withdrawal.

Brain tissue analysis of the socially isolated animals revealed
significantly lower than normal levels of gene transcription for
oligodendrocyte cells in the prefrontal cortex, a brain region
responsible for emotional and cognitive behavior.

"This research provides the first explanation of the mechanism
behind how this brain plasticity occurs," says Dietz, "showing how
this change in the level of social interaction of the adult animal
resulted in changes in oligodendrocytes."

The key change was that cellular nuclei in the prefrontal cortex
contained less heterochromatin, a tightly packed form of DNA
material, which is unavailable for gene expression.

"This process of DNA compaction is what signifies that the
oligodendrocytes have matured, allowing them to produce normal
amounts of myelin," says Dietz. "We have observed in socially
isolated animals that there isn't as much compaction, and the
oligodendrocytes look more immature. As adults age, normally, you
would see more compaction, but when social isolation interferes,
there's less compaction and therefore, less myelin being made."

She adds, however, that the research also showed that myelin
production went back to normal after a period of social
integration, suggesting that environmental intervention was
sufficient to reverse the negative consequences of adult social
isolation.

The new paper, together with a report published earlier this
year by another group showing myelin changes triggered by social
isolation early in life will broaden investigations into brain
plasticity, says David Dietz, PhD, one of the paper's co-authors,
an assistant professor of pharmacology and toxicology at UB.

In addition, adds Karen Dietz, the work has implications for
future questions regarding MS and other myelin disorders. "This
research suggests that maybe recovery from an MS episode might be
enhanced by social interaction," she says. "This opens another
avenue of investigation of how mood and myelin disorders may
interact with one another."

Major funding for the research came from the National Institutes
of Health.